Following the United States' acquisition of California from Mexico in 1848, a surge of new settlers from the east coast and Europe journeyed west to seek their fortunes in gold and make a new life. Dr. R.O. Tripp, a native of Massachusetts who arrived in 1849 to recover from an illness, was one of the early pioneers and probably the first Silicon Valley entrepreneur. He named the small town on the foothills of the Santa Cruz Mountains Woodside.

By 1852, a daily stagecoach service route between Woodside and San Francisco had already been created, attracting many new settlers to the booming lumber industry in the Santa Cruz Mountains. The lumber was used in the construction of San Francisco both before and after the Great 1906 earthquake.

The increasing number of lumbermen in the area allowed Dr. Tripp and his partners to establish the area's first general merchandise and supply store in 1854. Until the 1880s, when other commercial enterprises began to open in town and the growing nearby town of Redwood City by the bay, the Woodside Store was the center of the community's social activities.

Dr. Tripp's Woodside Store was the town's first "strip mall," with a bank with an armored safe and a dentist's practice where he extracted a tooth for $4 rather than $16 in San Francisco. He also established a saloon and a circulating library with 589 titles.

Tripp also made wine on a five-acre vineyard behind the store. He grew Burgundy, Grey Riesling, and Muscat grapes. He bottled and labeled the "San Mateo County Pioneer Brand" and sold over the counter at his Woodside store alongside E.H. Rixford's La Questa Cabernet.